Anxiety disorders and stressful events in Takotsubo syndrome

Background: Anxiety disorders are more common in Takotsubo syndrome (TS) than in acute coronary syndrome patients. The aim of this study was to investigate whether pre-existing anxiety disorders predispose to TS triggered by exclusively emotional stressful events.Methods: Triggering events were compared in 58 TS patients with and without pre-existing anxiety disorders; clinical, electrocardiographic and echocardiographic data were also collected.Results: Thirty-one (53%) patients had a previous history of anxiety disorders. The exclusively emotional stressful event-rate was higher in TS patients with pre-existing anxiety disorder (74% vs. 30%, p = 0.001), while TS caused by an undetermined trigger were significantly higher in patients without anxiety disorders (33% vs. 10%, p = 0.027). Moreover, in TS patients without a previous history of anxiety disorders, a trend of higher prevalence of physical events was found (16% vs. 37%, p = 0.07).Conclusions: In patients with pre-existing anxiety disorders, TS was predominantly triggered by exclusively emotional stressful events, thereby suggesting a possible relationship between anxiety and emotional cardiac frailty in TS patients

Microwave Ablation in Intermediate Hepatocellular Carcinoma in Cirrhosis: An Italian Multicenter Prospective Study

Background and Aims: To report long-term results in treatment of intermediate hepatocellular carcinoma (HCC) in cirrhotics using new high-powered microwaves (MWS) ablation alone. Methods: This multicenter study included 215 cirrhotics (age range: 67-84 years; 137 males; 149 Child A, 66 Child B) who underwent percutaneous ultrasound-guided high-powered MWS ablation instead of transarterial chemoembolization. Among the patient population, 109 had a single nodule (Ø 5.3-8 cm) [group A], 70 had 2 nodules (Ø 3-6 cm) [group B] and 36 had 3-5 nodules (Ø 1.5-6.8 cm) [group C]. MWS ablation efficacy was evaluated using enhanced-computed tomography and/or magnetic resonance imaging. Primary end-point was 5-year cumulative overall survival (OS). Results: On enhanced-computed tomography and/or magnetic resonance imaging, complete ablation rates were 100% for 1.5-3.5 cm nodules. In nodules >3.5-5 cm, it was 89% for the first ablation and 100% for the second. For lesions >5-8 cm, ablation was up to 92%. Overall, 1-, 3- and 5-year survival rates were 89, 60, and 21%, respectively. The cumulative OS rate of group A was 89%, 66% and 34% at 1, 3 and 5 years. The cumulative OS rate of group B was 88%, 60% and 11% at 1, 3 and 5 years. The cumulative OS rate of group C was 86%, 55% and 0%. The 5-year survival rate was significantly different among the groups (p <0.001). One patient died from rupture of HCC. Upon multivariate analysis, preablation total bilirubin >1.5 mg/dL was an independent factor for predicting lower survival. Conclusions: Percutaneous MWS ablation of intermediate HCC is safe and effective in inducing large volume of necrosis in intermediate HCC nodules, providing long-term survival rates similar to transarterial chemoembolization. Preablation total bilirubin >1.5 mg/dL as expression of liver function reserve is the main factor predicting a worse outcome

Origin of optical nonlinearity in plasmonic semiconductor nanostructures

The development of nanoscale nonlinear elements in photonic integrated circuits is hindered by the physical limits to the nonlinear optical response of dielectrics, which requires that the interacting waves propagate in transparent volumes for distances much longer than their wavelength. Here we present experimental evidence that optical nonlinearities in doped semiconductors are due to free-electron and their efficiency could exceed by several orders of magnitude that of conventional dielectric nonlinearities. Our experimental findings are supported by comprehensive computational results based on the hydrodynamic modeling, which naturally includes nonlocal effects, of the free-electron dynamics in heavily doped semiconductors. By studying third-harmonic generation from plasmonic nanoantenna arrays made out of heavily n-doped InGaAs with increasing levels of free-carrier density, we discriminate between hydrodynamic and dielectric nonlinearities. As a result, the value of maximum nonlinear efficiency as well as its spectral location can now be controlled by tuning the doping level. Having employed the common material platform InGaAs/InP that supports integrated waveguides, our findings pave the way for future exploitation of plasmonic nonlinearities in all-semiconductor photonic integrated circuits

anxiety disorders and stressful events in takotsubo syndrome

Background: Anxiety disorders are more common in Takotsubo syndrome (TS) than in acute coronary syndrome patients. The aim of this study was to investigate whether pre-existing anxiety disorders predispose to TS triggered by exclusively emotional stressful events. Methods: Triggering events were compared in 58 TS patients with and without pre-existing anxiety disorders; clinical, electrocardiographic and echocardiographic data were also collected. Results: Thirty-one (53%) patients had a previous history of anxiety disorders. The exclusively emotional stressful event-rate was higher in TS patients with pre-existing anxiety disorder (74% vs. 30%, p = 0.001), while TS caused by an undetermined trigger were significantly higher in patients without anxiety disorders (33% vs. 10%, p = 0.027). Moreover, in TS patients without a previous history of anxiety disorders, a trend of higher prevalence of physical events was found (16% vs. 37%, p = 0.07). Conclusions: In patients with pre-existing anxiety disorders, TS was predominantly triggered by exclusively emotional stressful events, thereby suggesting a possible relationship between anxiety and emotional cardiac frailty in TS patients

Next-generation sequencing comparative analysis of DNA mutations between blood-derived extracellular vesicles and matched cancer tissue in patients with IV grade glioblastoma

The biological heterogeneity of glioblastoma, IDH-wildtype (GBM, CNS WHO grade 4), the most aggressive type of brain cancer, is a critical hallmark, caused by changes in the genomic mutational asset and influencing clinical progression over time. The understanding and monitoring of the mutational profile is important not only to reveal novel therapeutic targets in this set of patients, but also to ameliorate the clinical stratification of subjects and the prognostic significance. As neurosurgery represents the primary technique to manage GBM, it is of utmost importance to optimize alternative and less invasive methods to monitor the dynamic mutation profile of these patients. Extracellular vesicles (EVs) are included in the liquid biopsy analysis and have emerged as the biological mirror of escaping and surviving mechanisms by many tumors, including glioblastoma. Very few studies have investigated the technical feasibility to detect and analyze the genomic profile by Next-Generation Sequencing (UMI system) in circulating EVs of patients with grade IV glioblastoma. Here, we attempted to characterize and to compare the corresponding matched tissue samples and potential variants with pathogenic significance of the DNA contained in peripheral-blood-derived EVs. The NGS analysis has revealed that patients with grade IV glioblastoma exhibited lesser DNA content in EVs than controls and that, both in EVs and matched cancer tissues, the NF1 gene was consistently mutated in all patients, with the c.2568C>G as the most common pathogenic variant expressed. This study supports the clinical utility of circulating EVs in glioblastoma as an eligible tool for personalized medicine

Effects of temperature and precipitation changes on shifts in breeding phenology of an endangered toad

Abstract In the last century, a plethora of species have shown rapid phenological changes in response to climate change. Among animals, amphibians exhibit some of the greatest responses since their activity strongly depends on temperature and rainfall regimes. These shifts in phenology can have negative consequences for amphibian fitness. Thus, understanding phenological changes in amphibians is pivotal to design conservation actions to mitigate climate change effects. We used data on Common Spadefoot Toad (Pelobates fuscus) reproductive migration to wetlands over a period of 8 years in Italy to (i) identify the factors related to breeding migrations, (ii) assess potential phenological shifts in the breeding period, and (iii) determine which climatic factors are related to the observed phenological shifts. Our results showed that toads migrate to spawning sites preferably in early spring, on rainy days with temperatures of 9–14 °C, and with high humidity. Furthermore, despite an increase in average temperature across the study period, we observed a delay in the start of breeding migrations of 12.4 days over 8 years. This counterintuitive pattern was the result of a succession of hot and dry years that occurred in the study area, highlighting that for ephemeral pond breeders, precipitation could have a larger impact than temperature on phenology. Our results belie the strong presumption that climate change will shift amphibian phenology toward an earlier breeding migration and underline the importance of closely investigating the environmental factors related to species phenology

Anxiety disorders and stressful events in Takotsubo syndrome

Background: Anxiety disorders are more common in Takotsubo syndrome (TS) than in acute coronary syndrome patients. Theaim of this study was to investigate whether pre-existing anxiety disorders predispose to TS triggered by exclusively emotional stressful events. Methods: Triggering events were compared in 58 TS patients with and without pre-existing anxiety disorders; clinical, electrocardiographic and echocardiographic data were also collected. Results: Thirty-one (53%) patients had a previous history of anxiety disorders. The exclusively emotional stressful event-rate was higher in TS patients with pre-existing anxiety disorder (74% vs. 30%, p = 0.001), while TS caused by an undetermined trigger were significantly higher in patients without anxiety disorders (33% vs. 10%, p = 0.027). Moreover, in TS patients without a previous history of anxiety disorders, a trend of higher prevalence of physical events was found (16% vs. 37%, p = 0.07). Conclusions: In patients with pre-existing anxiety disorders, TS was predominantly triggered by exclusively emotional stressful events, thereby suggesting a possible relationship between anxiety and emotional cardiac frailty in TS patients

Image_4_Molecular screening with liquid biopsy for anti-EGFR retreatment in metastatic colorectal cancer: preliminary data from the randomized phase 2 PARERE trial.jpeg

BackgroundRetreatment with anti-EGFR monoclonal antibodies is a promising strategy in patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who achieved benefit from previous anti-EGFR exposure upon exclusion of mutations in RAS/BRAF genes according to circulating tumor DNA (ctDNA) analysis by means of liquid biopsy (LB). This treatment approach is now being investigated in the randomized phase II trial PARERE (NCT04787341). We here present preliminary findings of molecular screening.MethodsPatients with RAS/BRAFV600E wt mCRC according to tissue genotyping who benefited from previous anti-EGFR-based treatment (fluoropyrimidines, oxaliplatin, irinotecan, and antiangiogenics) and then experienced disease progression to EGFR targeting were eligible for screening in the PARERE trial. The next-generation sequencing (NGS) panel Oncomine™ was employed for ctDNA testing.ResultsA total of 218 patients underwent LB, and ctDNA sequencing was successful in 201 of them (92%). RAS/BRAFV600E mutations were found in 68 (34%) patients and were mainly subclonal (median variant allele fraction [VAF] for KRAS, NRAS, and BRAF mutant clones: 0.52%, 0.62%, and 0.12%, respectively; p = 0.01), with KRASQ61H being the most frequently detected (31%). Anti-EGFR-free intervals did not predict ctDNA molecular status (p = 0.12). Among the 133 patients with RAS/BRAFV600E wt tumors according to LB, 40 (30%) harbored a mutation in at least another gene potentially implied in anti-EGFR resistance, mainly with subclonal expression (median VAF, 0.56%). In detail, alterations in PIK3CA, FBXW7, GNAS, MAP2K, ERBB2, BRAF (class I and II non-BRAFV600E), SMAD, EGFR, AKT1, and CTNNB1 occurred in 13%, 8%, 7%, 3%, 2%, 2%, 1%, 1%, 1%, and 1% cases, respectively. Co-mutations were detected in 13 (33%) out of 40 patients.ConclusionsThis is the largest prospective cohort of mCRC patients screened with LB for anti-EGFR retreatment in a randomized study. ctDNA genotyping reveals that at least one out of three patients candidate for retreatment should be excluded from this therapy, and other potential drivers of anti-EGFR resistance are found in approximately one out of three patients with RAS/BRAFV600E wt ctDNA.</p

Image_3_Molecular screening with liquid biopsy for anti-EGFR retreatment in metastatic colorectal cancer: preliminary data from the randomized phase 2 PARERE trial.jpeg

BackgroundRetreatment with anti-EGFR monoclonal antibodies is a promising strategy in patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who achieved benefit from previous anti-EGFR exposure upon exclusion of mutations in RAS/BRAF genes according to circulating tumor DNA (ctDNA) analysis by means of liquid biopsy (LB). This treatment approach is now being investigated in the randomized phase II trial PARERE (NCT04787341). We here present preliminary findings of molecular screening.MethodsPatients with RAS/BRAFV600E wt mCRC according to tissue genotyping who benefited from previous anti-EGFR-based treatment (fluoropyrimidines, oxaliplatin, irinotecan, and antiangiogenics) and then experienced disease progression to EGFR targeting were eligible for screening in the PARERE trial. The next-generation sequencing (NGS) panel Oncomine™ was employed for ctDNA testing.ResultsA total of 218 patients underwent LB, and ctDNA sequencing was successful in 201 of them (92%). RAS/BRAFV600E mutations were found in 68 (34%) patients and were mainly subclonal (median variant allele fraction [VAF] for KRAS, NRAS, and BRAF mutant clones: 0.52%, 0.62%, and 0.12%, respectively; p = 0.01), with KRASQ61H being the most frequently detected (31%). Anti-EGFR-free intervals did not predict ctDNA molecular status (p = 0.12). Among the 133 patients with RAS/BRAFV600E wt tumors according to LB, 40 (30%) harbored a mutation in at least another gene potentially implied in anti-EGFR resistance, mainly with subclonal expression (median VAF, 0.56%). In detail, alterations in PIK3CA, FBXW7, GNAS, MAP2K, ERBB2, BRAF (class I and II non-BRAFV600E), SMAD, EGFR, AKT1, and CTNNB1 occurred in 13%, 8%, 7%, 3%, 2%, 2%, 1%, 1%, 1%, and 1% cases, respectively. Co-mutations were detected in 13 (33%) out of 40 patients.ConclusionsThis is the largest prospective cohort of mCRC patients screened with LB for anti-EGFR retreatment in a randomized study. ctDNA genotyping reveals that at least one out of three patients candidate for retreatment should be excluded from this therapy, and other potential drivers of anti-EGFR resistance are found in approximately one out of three patients with RAS/BRAFV600E wt ctDNA.</p

Image_1_Molecular screening with liquid biopsy for anti-EGFR retreatment in metastatic colorectal cancer: preliminary data from the randomized phase 2 PARERE trial.jpeg

BackgroundRetreatment with anti-EGFR monoclonal antibodies is a promising strategy in patients with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC) who achieved benefit from previous anti-EGFR exposure upon exclusion of mutations in RAS/BRAF genes according to circulating tumor DNA (ctDNA) analysis by means of liquid biopsy (LB). This treatment approach is now being investigated in the randomized phase II trial PARERE (NCT04787341). We here present preliminary findings of molecular screening.MethodsPatients with RAS/BRAFV600E wt mCRC according to tissue genotyping who benefited from previous anti-EGFR-based treatment (fluoropyrimidines, oxaliplatin, irinotecan, and antiangiogenics) and then experienced disease progression to EGFR targeting were eligible for screening in the PARERE trial. The next-generation sequencing (NGS) panel Oncomine™ was employed for ctDNA testing.ResultsA total of 218 patients underwent LB, and ctDNA sequencing was successful in 201 of them (92%). RAS/BRAFV600E mutations were found in 68 (34%) patients and were mainly subclonal (median variant allele fraction [VAF] for KRAS, NRAS, and BRAF mutant clones: 0.52%, 0.62%, and 0.12%, respectively; p = 0.01), with KRASQ61H being the most frequently detected (31%). Anti-EGFR-free intervals did not predict ctDNA molecular status (p = 0.12). Among the 133 patients with RAS/BRAFV600E wt tumors according to LB, 40 (30%) harbored a mutation in at least another gene potentially implied in anti-EGFR resistance, mainly with subclonal expression (median VAF, 0.56%). In detail, alterations in PIK3CA, FBXW7, GNAS, MAP2K, ERBB2, BRAF (class I and II non-BRAFV600E), SMAD, EGFR, AKT1, and CTNNB1 occurred in 13%, 8%, 7%, 3%, 2%, 2%, 1%, 1%, 1%, and 1% cases, respectively. Co-mutations were detected in 13 (33%) out of 40 patients.ConclusionsThis is the largest prospective cohort of mCRC patients screened with LB for anti-EGFR retreatment in a randomized study. ctDNA genotyping reveals that at least one out of three patients candidate for retreatment should be excluded from this therapy, and other potential drivers of anti-EGFR resistance are found in approximately one out of three patients with RAS/BRAFV600E wt ctDNA.</p